Bioactive Materials 2 (2017) 248e252

Contents lists available at ScienceDirect

Bioactive Materials
journal homepage: http://www.keaipublishing.com/en/journals/
bioactive-materials/

Manufacturing of graded titanium scaffolds using a novel space holder

technique
Yunhui Chen a, *, Damon Kent a, b, c, Michael Bermingham a, c, Ali Dehghan-Manshadi a,
Gui Wang a, Cuie Wen d, Matthew Dargusch a, c
a
Queensland Centre for Advanced Materials Processing and Manufacturing (AMPAM), The University of Queensland, St. Lucia, 4072, Australia
b
School of Science and Engineering, University of the Sunshine Coast, Maroochydore DC, QLD, 4558, Australia
c
ARC Research Hub for Advanced Manufacturing of Medical Devices, Australia
d
School of Engineering, RMIT University, Melbourne, 3001, Australia

a r t i c l e i n f o a b s t r a c t

Article history: To optimize both the mechanical and biological properties of titanium for biomedical implants, a highly
Received 29 May 2017 flexible powder metallurgy approach is proposed to generate porous scaffolds with graded porosities and
Received in revised form pore sizes. Sugar pellets acting as space holders were compacted with titanium powder and then
5 July 2017
removed by dissolution in water before sintering. The morphology, pore structure, porosity and pore
Accepted 5 July 2017
interconnectivity were observed by optical microscopy and SEM. The results show that the porous ti-
Available online 18 July 2017
tanium has porosity levels and pore size gradients consistent with their design with gradual and smooth
transitions at the interfaces between regions of differing porosities and/or pore sizes. Meanwhile, the
Keywords:
Porous scaffolds
porous titanium has high interconnectivity between pores and highly spherical pore shapes. In this
Titanium article we show that this powder metallurgy processing technique, employing the novel sugar pellets as
Powder metallurgy space-holders, can generate porous titanium foams with well-controlled graded porosities and pore
Space holder sizes. This method has excellent potential for producing porous titanium structures for hard tissue en-
Graded porosity gineering applications.
© 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

1. Introduction Solid titanium and its alloys currently used in biomedical

The development of implants for hard tissue engineering such
as replacement of bone, teeth and joints is highly desired and has
shown enormous success in orthopaedic surgery. Porous synthetic
scaffolds are a highly promising new approach to repair and
remodel damaged bone tissue, replacing techniques using auto-
grafts (bone harvested from patient) or allografts (donor bone) [1,2]
as this technique can eliminate the potential disease transmission
from donor to recipient through autogenous bone grafts [3]. Tita-
nium and some of its alloys are considered to be the most attractive
metallic materials for biomedical applications [4] due to their
relatively low modulus, excellent strength-to-weight ratio, supe-
rior biocompatibility and corrosion resistance [5,6].
* Corresponding author.
E-mail address: y.chen18@uq.edu.au (Y. Chen).
Peer review under responsibility of KeAi Communications Co., Ltd.
implant applications have shown some limitations, such as lack of
osseointegration [7] and mismatch between the mechanical prop-
erties of the bone and the implant [8]. Porous titanium structures
have the potential to address these issues by providing a scaffold for
bone cell ingrowth [9] and by more closely matching the mechanical
properties of bone to alleviate stress-shielding effects [10]. How-
ever, structures with uniform porosity cannot satisfy all of the me-
chanical and biological requirements for implants due to their lack
of flexibility in tailoring their mechanical behaviors, biocompati-
bility and osseointegration to that of the bone. More suitable de-
signs could include porosity gradients to mimic that of the human
bone, from a dense, stiff external structure (the cortical bone) to a
porous internal one (the cancellous bone) with an appropriate de-
gree of pore interconnectivity [11]. Wen et al. [12] developed tita-
nium structures with porosity gradients with a solid core and highly
porous outer shell using powder metallurgy technique. Thieme et al.
[13] successfully manufactured titanium specimens using same
method with graded porosities which matched the designed

http://dx.doi.org/10.1016/j.bioactmat.2017.07.001
2452-199X/© 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 Y. Chen et al. / Bioactive Materials 2 (2017) 248e252
moduli. Titanium structures with graded porosities can be produced
by various processes such as pressure filtration, solid free-form
fabrication, multiple tape casting, etc. However, using these
methods it is difficult to control pore interconnectivity and pore
sizes [11].
In this study, a powder metallurgical process using sugar pellets
as space holders is explored for the fabrication of graded porous
titanium scaffolds with flexible porosity and pore size gradients.
We demonstrated that titanium scaffolds can be manufactured
with the predesigned graded porosities and pore sizes, while
maintaining high levels of interconnectivity and spherical pore
shapes for biomedical applications.
2. Materials and methodology
Titanium hydride-dehydride powder (>99.9% purity) with particle
size of approximately 45 mm was used as a base powder due to its high
sinterability. Spherical sugar pellets, (supplied by JF-Pharmaland
Technology Development Co., Ltd, China) were used as the space
holder. Three pellet size distributions, namely 0.212e0.355 mm,
0.3e0.425 mm and 0.425e0.5 mm, were chosen to generate porosity
gradients in the compacts. Spherical pellets sized were chosen ac-
cording to Loh et al.'s [14] review on the pore size and biocompati-
bility. Two different structures with gradient porosities were chosen
to demonstrate the powder metallurgical process (as shown in Fig. 1).
With the help of a temporary mould to maintain shape during
die filling, gradient structures were created as illustrated in Fig. 1(C).
After removal of the mould, the sample was pressed at 400 MPa to
acquire cylindrical green compacts of 15 mm in diameter and 10 mm
in height. High compaction pressure of 400 MPa was employed to
eliminate sample deformation during dissolution of the sugar pellet
space holder. The space holder was dissolved by distilled water at
temperatures of 70e80
C with constant stirring using a magnetic
stirrer. The dissolution time was 4 h and the water was changed
twice to ensure thorough removal of the sugar pellets from the
green compacts. Samples were then dried in an oven at 90
C for 2 h.
Sintering was carried out in a high vacuum furnace at 1300
C for
2 h at a vacuum pressure of 105 Torr. In order to prevent contam-
ination, all samples were placed on an Al2O3 ceramic disc for sin-
tering. Samples were sectioned and polished for analysis of
microstructure and surface morphologies. The porous structure and
interconnectivity were evaluated by optical microscopy and SEM.
The density and porosity of the sintered compacts was determined
by the Archimedes method with oil impregnation. H-Galden ZT-180
was used instead of water to give more accurate results. The density
of the sintered sample r and porosity P Open , were calculated using:
rHG  W Air
r¼
W Oil  W HG
rHG ðW Oil  W Air Þ
P Open ¼  100
rOil ðW Oil  W HG Þ
where rHG is the density of the H-Galden (1.69 g/mL at 21
C), rOil is
the density of the oil used (KS7470, density 0.885 g/mL), WAir is the
dry weight of the compact, WOil is the weight of the compact after
oil infiltration, and WHG is the weight of the oil infiltrated compact
measured while immersed in H-Galden. The mechanical properties
of the porous structures were measured with an Instron 5584 test
machine. The properties are listed in Table 1. The elements of the
specimen was determined with inductively coupled plasma optical
emission spectrometry (ICP-OES), using Spectro-Arcos equipment.
Carbon content was determined by carrier gas hot extraction using
a LECO CS600 gas analyzer (see Table 2).
249
3. Results and discussion
Porous titanium foam with porosity gradients and high integrity
were achieved, as shown in Fig. 2. Sintered compacts were
sectioned in half to reveal the interior of the porous structures. The
sintered compacts exhibit mechanically stable edges and surface,
with little deformation and no degradation evident during the
sugar pellet dissolution and sintering process. The interior porous
structure of the sintered samples is presented in Fig. 3, as obtained
by optical microscopy. Pore morphology and size can be clearly
observed from the image. The space-holding particles have been
completely removed. ICP-OES results showed that the residual
carbon is only 0.01 wt%.
Image J was used to analyse the pore geometry after sintering.
The sugar pellet space holders produced well-defined pore sizes
which are reasonably spherical and uniform in shape. The porosity
and pore size changes which are consistent with the predesigned
models can be clearly observed and the transitions between regions
of differing porosities are smooth with no traces of cracking. It is
noted that slight deformation of the long cylindrical sample in
Fig. 2(a) is observed due to the compact-and-sinter process. Higher
compaction pressure would reduce the deformation.
Fig. 4 shows the SEM images of the pore structures and the
interface between regions of differing porosities with a gradient of
porosity. As shown in Fig. 4(a), the pores created by the sugar pellets
are highly spherical and uniform in shape. Fig. 4(b) shows there is a
high degree of interconnectivity between pores and that the pores
have a relatively rough inner surface associated with the morphology
of the sugar pellet space holders, especially at the interconnections.
This rough surface is expected to increase the adhesion-attachment
rate of cells for bone ingrowth [9]. Sugar pellets, which are comprised
of sugar and starch, are materials considered to be very safe in the
human body. After sintering, any residue from the space-holding
materials will break down into carbon or form TiC particles which
are considered harmless to human tissue [16]. However, it may in-
fluence the mechanical properties of the scaffolds. Inductively
coupled plasma optical emission spectrometry (ICP-OES) results
show that the residual C is only 0.01 wt%. Further studies are
necessary to understand their influence on the properties and per-
formance of the porous foam structures (see Fig. 5).
The main goal in the design and fabrication of an orthopaedic
scaffold is to restore the function of the native tissue that is to be
replaced. The ideal implant should be biocompatible, possess
adequate mechanical properties to support the applied physiolog-
ical load, be corrosion/wear resistant and finally show good bioac-
tivity to ensure sufficient bonding at the material/bone interface.
The manufacturing route demonstrated in this paper has been
shown to produce porous titanium structures with highly spherical
(1) pore shapes, well-controlled pore size and porosity, and high
interconnectivity [17]. The porous titanium scaffolds have excellent
potential for hard tissue engineering applications. This powder
metallurgical process using a sugar pellet as space holders can be
(2)
used to fabricate graded porous structures that can facilitate bone
ingrowth and effectively enable variation of the Young's modulus
across the structures [18]. The elastic moduli of the porous samples
is 18.5, 16.4 and 12.1 GPa for 30%, 40% and 50% porosity, respectively.
This is consistent with the characteristics of natural bone, which
typically has a stiffness of 0.1e20 GPa [1]. The yield strengths of the
scaffolds, are 89.8, 176.5 and 202.3 GPa respectively, and with the
exception of the one with 50% designed porosity, are superior to that
of natural bone (130e180 MPa) [4]. In this regard, as the porosity
and pore size can be well-controlled, we have planned FEM simu-
lations to optimize the structural design to maximize the interaction
between the implant and the surrounding bone. The techniques
outlined in this work offer a stepwise improvement over other
250 Y. Chen et al. / Bioactive Materials 2 (2017) 248e252

Fig. 1. Schematic of designed structures with porosity gradients: (A) a structure with three layers of different porosities, (b) a structure with differing interior porosity, and (C) the
process of generate porosity gradient using temporary mould. PM No.1 and PM No.2 are two different kind of titanium and sugar pellets mixture to create gradients. For instance,
30% sugar pellets mixture with pore size 0.212e0.355 mm and 50% sugar pellets mixture with pore size 0.425e0.5 mm as shown in (b).

Table 1
Sintered titanium scaffold properties using sugar pellets as space holder. assisted liquid-phase sintering (LPS) to fabricate porous titanium
structures with elastic modulus matching the targeted modulus of
Designed porosity using sugar pellets, % 30 40 50
design, but the biocompatibility of these materials is still ques-
Open porosity (%) 2.23 7.77 11.32 tionable and the pore sizes are too small to allow full growth of
Open to total porosity ratio [15] (%) 11.09 28.79 35.52
Harversian units [13]. The precise control of pore size and flexibility
Density (g/cm3) 3.60 3.29 3.07
Elastic Modulus (E), (GPa) 18.5 16.4 12.1 in pore gradients demonstrated in the present study can overcome
Yield strength (sy ), (GPa) 89.8 176.5 202.3 the constraints imposed by the other fabrication methods as well as
remove the requirement for surface coating/roughening processes
[9] currently used to encourage material/bone bonding.
powder metallurgy based methods [12], which do not offer the Powder sintering, employing spherical pharmaceutical sugar
same degree of control of the porosity, pore size and inter- pellets as a new form of space holder material, has been shown to
connectivity between pores. Thieme et al. reported a silicon- be an ideal processing technique as it allows customization of
material properties and production of net or near-net shape com-
ponents. It also allows easily adjustment of porosities, pore sizes
Table 2 and levels of interconnectivity between pores.
Chemical analysis of the titanium powder and manufactured scaffold.

ICP-OES/LECO Ti Cb Ob Nb 4. Conclusions
Titanium powder (wt%) Balanced <0.01 0.12 0.02
Scaffold with 50% porosity (wt%) Balanced 0.01 0.27 0.30 Porous titanium structures with graded porosity and varying
a
Analyzed by inductively coupled plasma optical emission spectroscopy (ICP-OES). pore sizes have been manufactured by powder metallurgy using
b
Analyzed by a carrier gas hot extraction gas analyzer. sugar pellets as a space holder. It was demonstrated that pore sizes,
 Y. Chen et al. / Bioactive Materials 2 (2017) 248e252 251

Fig. 2. Morphology of the porous structure.

Fig. 3. Sintered titanium foam structures: (A) a porous structure with layers of differing porosities, and (B) porous structures with a solid shell/internal porosity and solid interior/
porous shell.

Fig. 4. Interface between regions of different porosities: (A) interfaces of regions with 60% porosity (0.3e0.425 mm pore size) (region a), 40% porosity (0.425e0.5 mm pore size)
(region b) and 50% porosity (0.212e0.355 mm Pore size) (region c), (B) interface between regions with 40% porosity (0.425e0.5 mm pore size) (region a) and 60% porosity
(0.3e0.425 mm) (region b), (C) interface between solid shell and porous interior with 50% porosity (0.3e0.425 mm pore size, and (D) interface between porous shell with 50%
porosity (0.3e0.425 mm pore size) and solid core.

porosities and porosity gradients can be effectively controlled by biocompatibility for hard tissue engineering applications. The
varying the sugar pellets sizes, volume fractions and pressing order. techniques developed are highly flexible and can be applied to the
The sintered titanium scaffolds with graded porosities have the manufacture of porous structures with varying porosities, pore
potential to deliver optimized mechanical properties with excellent sizes and geometries.
252 Y. Chen et al. / Bioactive Materials 2 (2017) 248e252
Fig. 5. SEM images of the porous titanium: (A) morphology of pores, including micro pores, (B) interconnectivity between pores.
Acknowledgments
The authors acknowledge the support of Queensland Centre for
Advanced Materials Processing and Manufacturing (AMPAM). M.
Dargusch acknowledges the support of the ARC Research Hub for
Advanced Manufacturing of Medical Devices (IH150100024). M.J.
Bermingham acknowledges the support of the ARC Discovery Early
Career Researcher Awards (DE160100260).
References
[1] P. Lichte, H.C. Pape, T. Pufe, P. Kobbe, H. Fischer, Scaffolds for bone healing:
concepts, materials and evidence, Injury 42 (2011) 569e573, http://
dx.doi.org/10.1016/j.injury.2011.03.033.
[2] S. Bose, M. Roy, A. Bandyopadhyay, Recent advances in bone tissue engi-
neering scaffolds, Trends Biotechnol. 30 (2012) 546e554, http://dx.doi.org/
10.1016/j.tibtech.2012.07.005.
[3] C. Myeroff, M. Archdeacon, Autogenous bone graft: donor sites and tech-
niques, J. Bone Jt. Surg. Am. 93 (2011) 2227e2236, http://dx.doi.org/10.2106/
JBJS.J.01513.
[4] C.N. Elias, J.H.C. Lima, R. Valiev, M.A. Meyers, Biomedical applications of tita-
nium and its alloys, J. Min. Met. Mater. Soc. (2008) 46e49, http://dx.doi.org/
10.1007/s11837-008-0031-1.
[5] Y. Li, C. Yang, H. Zhao, S. Qu, X. Li, Y. Li, New developments of ti-based alloys
for biomedical applications, Mater. (Basel) 7 (2014) 1709e1800, http://
dx.doi.org/10.3390/ma7031709.
[6] V.S. De Viteri, E. Fuentes, Titanium and titanium alloys as biomaterials chapter,
Tribol. - Fundam. Adv. (2013) 155e182, http://dx.doi.org/10.5772/3427.
[7] J. Gallo, J. Vaculova, S.B. Goodman, Y.T. Konttinen, J.P. Thyssen, Contributions
of human tissue analysis to understanding the mechanisms of loosening and
osteolysis in total hip replacement, Acta Biomater. 10 (2014) 2354e2366,
http://dx.doi.org/10.1016/j.actbio.2014.02.003.
[8] V. Goriainov, R. Cook, J.M. Latham, D.G. Dunlop, R.O.C. Oreffo, Bone and metal:
an orthopaedic perspective on osseointegration of metals, Acta Biomater. 10
(2014) 4043e4057, http://dx.doi.org/10.1016/j.actbio.2014.06.004.
[9] S.K. Nishimoto, M. Nishimoto, S.-W. Park, K.-M. Lee, H.-S. Kim, J.-T. Koh, et al.,
The effect of titanium surface roughening on protein absorption, cell attach-
ment, and cell spreading, Int. J. Oral Maxillofac. Implants 23 (2007) 675e680.
http://www.ncbi.nlm.nih.gov/pubmed/18807564.
[10] B. Dabrowski, W. Swieszkowski, D. Godlinski, K.J. Kurzydlowski, Highly porous
titanium scaffolds for orthopaedic applications, J. Biomed. Mater. Res. - Part B
Appl. Biomater. 95 (2010) 53e61, http://dx.doi.org/10.1002/jbm.b.31682.
[11] X. Miao, D. Sun, Graded/gradient porous biomaterials, Mater. (Basel) 3 (2009)
26e47, http://dx.doi.org/10.3390/ma3010026.
[12] C.E. Wen, Y. Yamada, A. Nouri, P. Hodgson, Porous titanium with porosity
gradients for biomedical applications, Mater. Sci. Forum 539e543 (2007)
720e725, http://dx.doi.org/10.4028/www.scientific.net/MSF.539-543.720.
[13] M. Thieme, K.P. Wieters, F. Bergner, D. Scharnweber, H. Worch, J. Ndop, et al.,
Titanium powder sintering for preparation of a porous functionally graded
material destined for orthopaedic implants, J. Mater. Sci. Mater. Med. 12
(2001) 225e231, http://dx.doi.org/10.1023/A:1008958914818.
[14] Q.L. Loh, C. Choong, Three-dimensional scaffolds for tissue engineering ap-
plications: role of porosity and pore size, Tissue Eng. Part B. Rev. 19 (2013)
485e502, http://dx.doi.org/10.1089/ten.TEB.2012.0437.
[15] M.P. Albano, L.B. Garrido, K. Plucknett, L.A. Genova, Processing of porous
yttria-stabilized zirconia tapes: influence of starch content and sintering
temperature, Ceram. Int. 35 (2009) 1783e1791, http://dx.doi.org/10.1016/
j.ceramint.2008.10.003.
[16] Y. Cheng, Y.F. Zheng, Characterization of TiN, TiC and TiCN Coatings on
Tie50.6 at.% Ni Alloy Deposited by PIII and Deposition Technique, 2006,
http://dx.doi.org/10.1016/j.surfcoat.2006.07.216.
[17] Y. Chen, D. Kent, M. Bermingham, A. Dehghan-Manshadi, M. Dargusch,
Manufacturing of biocompatible porous titanium scaffolds using a novel
spherical sugar pellet space holder, Mater. Lett. 195 (2017) 92e95, http://
dx.doi.org/10.1016/j.matlet.2017.02.092.
[18] N. Tuncer, G. Arslan, E. Maire, L. Salvo, Investigation of spacer size effect on
architecture and mechanical properties of porous titanium, Mater. Sci. Eng. A
530 (2011) 633e642, http://dx.doi.org/10.1016/j.msea.2011.10.036.